Modulation of the fecal bile acid profile by gut microbiota in cirrhosis

J Hepatol. 2013 May;58(5):949-55. doi: 10.1016/j.jhep.2013.01.003. Epub 2013 Jan 16.


Background & aims: The 7α-dehydroxylation of primary bile acids (BAs), chenodeoxycholic (CDCA) and cholic acid (CA) into the secondary BAs, lithocholic (LCA) and deoxycholic acid (DCA), is a key function of the gut microbiota. We aimed at studying the linkage between fecal BAs and gut microbiota in cirrhosis since this could help understand cirrhosis progression.

Methods: Fecal microbiota were analyzed by culture-independent multitagged-pyrosequencing, fecal BAs using HPLC and serum BAs using LC-MS in controls, early (Child A) and advanced cirrhotics (Child B/C). A subgroup of early cirrhotics underwent BA and microbiota analysis before/after eight weeks of rifaximin.

Results: Cross-sectional: 47 cirrhotics (24 advanced) and 14 controls were included. In feces, advanced cirrhotics had the lowest total, secondary, secondary/primary BA ratios, and the highest primary BAs compared to early cirrhotics and controls. Secondary fecal BAs were detectable in all controls but in a significantly lower proportion of cirrhotics (p<0.002). Serum primary BAs were higher in advanced cirrhotics compared to the rest. Cirrhotics, compared to controls, had a higher Enterobacteriaceae (potentially pathogenic) but lower Lachonospiraceae, Ruminococcaceae and Blautia (7α-dehydroxylating bacteria) abundance. CDCA was positively correlated with Enterobacteriaceae (r=0.57, p<0.008) while Ruminococcaceae were positively correlated with DCA (r=0.4, p<0.05). A positive correlation between Ruminococcaceae and DCA/CA (r=0.82, p<0.012) and Blautia with LCA/CDCA (r=0.61, p<0.03) was also seen. Prospective study: post-rifaximin, six early cirrhotics had reduction in Veillonellaceae and in secondary/primary BA ratios.

Conclusions: Cirrhosis, especially advanced disease, is associated with a decreased conversion of primary to secondary fecal BAs, which is linked to abundance of key gut microbiome taxa.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Infective Agents / therapeutic use
  • Bile Acids and Salts / analysis*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae / physiology
  • Feces / chemistry*
  • Female
  • Humans
  • Intestines / microbiology*
  • Liver Cirrhosis / metabolism*
  • Male
  • Microbiota / physiology*
  • Middle Aged
  • Prospective Studies
  • Rifamycins / therapeutic use
  • Rifaximin
  • Ruminococcus / isolation & purification
  • Ruminococcus / physiology
  • Veillonellaceae / isolation & purification
  • Veillonellaceae / physiology


  • Anti-Infective Agents
  • Bile Acids and Salts
  • Rifamycins
  • Rifaximin